Amyloid β Protein Precursor Is Phosphorylated by JNK-1 Independent of, yet Facilitated by, JNK-Interacting Protein (JIP)-1

Meir H. Scheinfeld, Enrico Ghersi, Peter Davies, Luciano D'Adamio

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is genetically linked to the processing of amyloid β protein precursor (AβPP). Aside from being the precursor of the amyloid β (Aβ) found in plaques in the brains of patients with AD, little is known regarding the functional role of AβPP. We have recently reported biochemical evidence linking AβPP to the JNK signaling cascade by finding that JNK-interacting protein-1 (JIP-1) binds AβPP. In order to study the functional implications of this interaction we assayed the carboxyl-terminal of AβPP for phosphorylation. We found that the threonine 668 within the AβPP intracellular domain (AID or elsewhere AICD) is indeed phosphorylated by JNK1. We surprisingly found that although JIP-1 can facilitate this phosphorylation, it is not required for this process. We also found that JIP-1 only facilitated phosphorylation of AβPP but not of the two other family members APLP1 (amyloid precursor-like protein 1) and APLP2. Understanding the connection between AβPP phosphorylation and the JNK signaling pathway, which mediates cell response to stress may have important implications in understanding the pathogenesis of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)42058-42063
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number43
DOIs
StatePublished - Oct 24 2003

Fingerprint

Amyloid beta-Protein Precursor
Phosphorylation
Proteins
Alzheimer Disease
Serum Amyloid A Protein
Threonine
MAP Kinase Signaling System
Amyloid
Brain
Processing

ASJC Scopus subject areas

  • Biochemistry

Cite this

Amyloid β Protein Precursor Is Phosphorylated by JNK-1 Independent of, yet Facilitated by, JNK-Interacting Protein (JIP)-1. / Scheinfeld, Meir H.; Ghersi, Enrico; Davies, Peter; D'Adamio, Luciano.

In: Journal of Biological Chemistry, Vol. 278, No. 43, 24.10.2003, p. 42058-42063.

Research output: Contribution to journalArticle

@article{6bede13be1054586bbe934ab30e79349,
title = "Amyloid β Protein Precursor Is Phosphorylated by JNK-1 Independent of, yet Facilitated by, JNK-Interacting Protein (JIP)-1",
abstract = "Alzheimer's disease (AD) is genetically linked to the processing of amyloid β protein precursor (AβPP). Aside from being the precursor of the amyloid β (Aβ) found in plaques in the brains of patients with AD, little is known regarding the functional role of AβPP. We have recently reported biochemical evidence linking AβPP to the JNK signaling cascade by finding that JNK-interacting protein-1 (JIP-1) binds AβPP. In order to study the functional implications of this interaction we assayed the carboxyl-terminal of AβPP for phosphorylation. We found that the threonine 668 within the AβPP intracellular domain (AID or elsewhere AICD) is indeed phosphorylated by JNK1. We surprisingly found that although JIP-1 can facilitate this phosphorylation, it is not required for this process. We also found that JIP-1 only facilitated phosphorylation of AβPP but not of the two other family members APLP1 (amyloid precursor-like protein 1) and APLP2. Understanding the connection between AβPP phosphorylation and the JNK signaling pathway, which mediates cell response to stress may have important implications in understanding the pathogenesis of Alzheimer's disease.",
author = "Scheinfeld, {Meir H.} and Enrico Ghersi and Peter Davies and Luciano D'Adamio",
year = "2003",
month = "10",
day = "24",
doi = "10.1074/jbc.M304853200",
language = "English (US)",
volume = "278",
pages = "42058--42063",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "43",

}

TY - JOUR

T1 - Amyloid β Protein Precursor Is Phosphorylated by JNK-1 Independent of, yet Facilitated by, JNK-Interacting Protein (JIP)-1

AU - Scheinfeld, Meir H.

AU - Ghersi, Enrico

AU - Davies, Peter

AU - D'Adamio, Luciano

PY - 2003/10/24

Y1 - 2003/10/24

N2 - Alzheimer's disease (AD) is genetically linked to the processing of amyloid β protein precursor (AβPP). Aside from being the precursor of the amyloid β (Aβ) found in plaques in the brains of patients with AD, little is known regarding the functional role of AβPP. We have recently reported biochemical evidence linking AβPP to the JNK signaling cascade by finding that JNK-interacting protein-1 (JIP-1) binds AβPP. In order to study the functional implications of this interaction we assayed the carboxyl-terminal of AβPP for phosphorylation. We found that the threonine 668 within the AβPP intracellular domain (AID or elsewhere AICD) is indeed phosphorylated by JNK1. We surprisingly found that although JIP-1 can facilitate this phosphorylation, it is not required for this process. We also found that JIP-1 only facilitated phosphorylation of AβPP but not of the two other family members APLP1 (amyloid precursor-like protein 1) and APLP2. Understanding the connection between AβPP phosphorylation and the JNK signaling pathway, which mediates cell response to stress may have important implications in understanding the pathogenesis of Alzheimer's disease.

AB - Alzheimer's disease (AD) is genetically linked to the processing of amyloid β protein precursor (AβPP). Aside from being the precursor of the amyloid β (Aβ) found in plaques in the brains of patients with AD, little is known regarding the functional role of AβPP. We have recently reported biochemical evidence linking AβPP to the JNK signaling cascade by finding that JNK-interacting protein-1 (JIP-1) binds AβPP. In order to study the functional implications of this interaction we assayed the carboxyl-terminal of AβPP for phosphorylation. We found that the threonine 668 within the AβPP intracellular domain (AID or elsewhere AICD) is indeed phosphorylated by JNK1. We surprisingly found that although JIP-1 can facilitate this phosphorylation, it is not required for this process. We also found that JIP-1 only facilitated phosphorylation of AβPP but not of the two other family members APLP1 (amyloid precursor-like protein 1) and APLP2. Understanding the connection between AβPP phosphorylation and the JNK signaling pathway, which mediates cell response to stress may have important implications in understanding the pathogenesis of Alzheimer's disease.

UR - http://www.scopus.com/inward/record.url?scp=0142211267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142211267&partnerID=8YFLogxK

U2 - 10.1074/jbc.M304853200

DO - 10.1074/jbc.M304853200

M3 - Article

VL - 278

SP - 42058

EP - 42063

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 43

ER -